Evaluating differential item functioning in the EQ-5D-5L in acute ischemic stroke

BackgroundHealth-related quality of life is a key secondary endpoint in stroke trials. Differential item functioning (DIF) occurs when individuals with the same underlying HRQOL interpret and respond differently to questionnaire items due to group characteristics, potentially biasing treatment comparisons. This study evaluates DIF in the patient-reported five-level EuroQOL (EQ-5D-5L) among patients with acute ischemic stroke across age, sex, and treatment groups. MethodsData were obtained from the AcT trial, a registry-based randomized comparison of alteplase and tenecteplase. Patients completed the EQ-5D-5L at 90 days post-stroke. DIF was assessed using multigroup graded response models with the Wald-based sweep procedure, which accounts for between-group differences in latent trait distributions. We quantified effect sizes using signed weighted area between curves (sWABC), considering |sWABC| <0.10 as negligible. ResultsAmong 1,264 patients (51.2% tenecteplase; 46.5% female; 30.1% aged [&ge;]80). Omnibus testing revealed significant DIF only for age (X{superscript 2} = 86.9, p < 0.001); neither sex (X{superscript 2} = 31.7, p = 0.063) nor treatment (X{superscript 2} = 22.4, p = 0.379) showed evidence of DIF. At the item level, four items flagged for age-related DIF: self-care, usual activities, pain/discomfort, and anxiety/depression. However, only self-care (sWABC = -0.46) and usual activities (sWABC = - 0.34) showed moderate effects, while pain/discomfort (sWABC = -0.002) and anxiety/depression (sWABC = 0.09) were negligible. Importantly, factor scores from models with and without DIF adjustment correlated (correlation coefficient = 0.98). ConclusionsThe EQ-5D-5L appears to function equivalently across sex and treatment groups in this stroke population. Age-related DIF, though statistically detectable in physical functioning items, had little practical consequence for individual scores, findings that support the instruments use for HRQOL comparisons in stroke trials. RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.